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Polyamines added extracellularly to intestinal and vascular smooth muscle cells cause relaxation through inhibition of Ca2+ channel activity. Intracellularly applied polyamines also affect Ca2+ channel properties. Polyamines do not readily pass over the plasma membrane because of their positive charges but in permeabilized smooth muscle preparations they have free access to the cytoplasm. In this system they increase sensitivity of the contractile machinery to Ca2+ through inhibition of myosin phosphatase activity. The magnitude of Ca2+ channel and phosphatase inhibition depends on the number of positive charges on the polyamine molecule. Polyamines have an obligatory, but yet undefined, role in regulation of cell growth and proliferation. Several groups of protein kinases, such as tyrosine and mitogen activated protein (MAP)-kinases transmit the growth signal from the plasma membrane to the cell nucleus where mitosis and protein synthesis are initiated. The data reviewed here show that polyamines may affect such signal transmission via inhibition of phosphatase activity.

Effects of the naturally occurring polyamine spermine on electrical and contractile properties of the rat portal vein were studied. 1 mM spermine nearly abolished spike activity and spontaneous contractions and decreased the intracellular Ca2+ concentration ([Ca2+]i). The phasic force responses to 0.1 and 1 microM phenylephrine were partially inhibited, but not the sustain plateau contraction caused by 5 microM phenylephrine. The Ca(2+)-force relation in high-K+ (128 mM)-depolarized veins was shifted to the right, EC50 for Ca2+ increasing from 0.50 +/- 0.03 mM (control, n = 8) to 0.65 +/- 0.06 and to 0.94 +/- 0.03 at 1 (n = 4) and 10 (n = 3) mM spermine, respectively. However, at a Ca2+ concentration of 2.5 mM, giving maximal force, there was no effect of spermine (1 mM) on either force or [Ca2+]i. Whereas extracellular spermine thus reduced contractile activity at moderate levels of stimulation, increased intracellular concentration of spermine potentiated the force response to Ca2+. Intracellular loading of spermine by reversible permeabilization increased its concentration by 2-3 times. The spontaneous activity and response to phenylephrine were unchanged. However, the Ca(2+)-force relation of depolarized veins was shifted to the left, EC50 decreasing from 0.51 +/- 0.04 mM in controls (n = 7) to 0.36 +/- 0.02 mM in the loaded veins (n = 9). Spermine increased Ca(2+)-activated force in portal veins permeabilized with beta-escin. The degree of potentiation was consistent with observed effects in spermine-loaded intact veins. The results suggest that spermine at physiological intracellular concentration may contribute to the determination of Ca2+ sensitivity in vascular smooth muscle cells.